Acute Mixed Lineage Leukemia With an inv(8)(p11q13) Resulting in Fusion of the Genes for MOZ and TIF2

Liang, Jian; Prouty, Leonard; Williams, B. Jill; Dayton, Mark A.; Blanchard, Kerry

doi:10.1182/blood.v92.6.2118.418k09_2118_2122

Cited by 35 publications

(30 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The monocytic leukemia zinc finger protein (MOZ) is a MYST-type HAT and functions as a co-activator of the AML1 transcription factor (8,27). MOZ is involved in leukemia-associated chromosome rearrangements such as t(8;16)(p11;p13) (26), t (8;22) (27,28), and inv (8) (29,30), which result in fusion of MOZ to the transcriptional co-activators CBP, p300, and TIF2, respectively. Although MOZ and p300/CBP act as co-activators for AML1, MOZ-CBP inhibits AML1-mediated transcription (28,31,32).…”

mentioning

confidence: 99%

Monocytic Leukemia Zinc Finger (MOZ) Interacts with p53 to Induce p21 Expression and Cell-cycle Arrest

Rokudai

Aikawa

Tagata

et al. 2009

Journal of Biological Chemistry

View full text Add to dashboard Cite

Upon DNA damage, p53 can induce either cell-cycle arrest or apoptosis. Here we show that monocytic leukemia zinc finger (MOZ) forms a complex with p53 to induce p21 expression and cell-cycle arrest. The levels of the p53-MOZ complex increased in response to DNA damage to levels that induce cell-cycle arrest. MOZ(-/-) mouse embryonic fibroblasts failed to arrest in G1 in response to DNA damage, and DNA damage-induced expression of p21 was impaired in MOZ(-/-) cells. These results suggest that MOZ is involved in regulating cell-cycle arrest in the G1 phase. Screening of tumor-associated p53 mutants demonstrated that the G279E mutation in p53 disrupts interactions between p53 and MOZ, but does not affect the DNA binding activity of p53. The leukemia-associated MOZ-CBP fusion protein inhibits p53-mediated transcription. These results suggest that inhibition of p53/MOZ-mediated transcription is involved in tumor pathogenesis and leukemogenesis.

show abstract

mentioning

confidence: 99%

Monocytic Leukemia Zinc Finger (MOZ) Interacts with p53 to Induce p21 Expression and Cell-cycle Arrest

Rokudai

Aikawa

Tagata

et al. 2009

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…The chimaeric MOZ fusion protein consists of the HAT domain of MOZ and the majority of the CBP/p300 protein. Indirect recruitment of CBP was also reported to be associated with the MOZ‐TIF2 leukaemic fusion whereby MOZ is fused with the transactivation domains of TIF2 (Transcription intermediary factor 2) [144,145]. MOZ‐TIF2 transformed haematopoietic progenitor cells in vitro and was able to induce AML in vivo.…”

Section: Deregulation Of the Epigenetic Writersmentioning

confidence: 98%

Transcriptional and epigenetic networks in haematological malignancy

Cheung

2011

FEBS Letters

View full text Add to dashboard Cite

a b s t r a c tIdentification of transcription factors as prevalent targets affected by recurring chromosomal translocations has provided the first hint for the importance of transcriptional deregulation in haematological malignancies. However, the actual molecular functions of these leukaemia-associated transcription factors on gene expression remained largely unknown until the recent discovery of their association with specific enzymatic activities that modify epigenetic codes (at DNA and/or histone levels) of downstream transcriptional targets. Intriguingly, while only just about half of acute leukaemia associates with recurring translocations, emerging evidence indicates that cryptic mutations identified in the ''normal-karyotype'' leukaemia also frequently affect components of epigenetic machinery. We will review these recent findings and discuss their implications in understanding the biology of the disease and in development of effective cancer therapeutics.

show abstract

“…MOZ was first identified as a gene involved in the translocation t(8;16)(p11;p13) resulting in the MOZ–CBP fusion gene. ( 11 ) The MOZ–p300 , MOZ–TIF2 and MOZ–NcoA3 fusion genes were later identified in AML from t(8;22)(p11;q13), ( 12,13 ) inv(8)(p11;q13) ( 14,15 ) and t(8; 20)(p11;q13), ( 16 ) respectively (Fig. 1).…”

Section: Involvement Of the Moz Gene In Chromosomal Translocationsmentioning

confidence: 99%

Roles of the histone acetyltransferase monocytic leukemia zinc finger protein in normal and malignant hematopoiesis

Katsumoto¹,

Yoshida²,

Kitabayashi³

2008

Cancer Science

View full text Add to dashboard Cite

In acute myeloid leukemia (AML), fusion genes often form as the result of specific chromosomal translocations.(1,2) Many of these fused genes, including MOZ, are transcription-related factors involved in the development or self-renewal of hematopoietic stem cells (HSC) and/or in hematopoietic cell differentiation. (3,4) Monocytic leukemia zinc finger protein (MOZ) is a Myst (MOZ, Ybf2 (Sas3), Sas2, Tip60)-type histone acetyltranseferase (HAT) that functions as a transcriptional coactivator for hematopoietic transcription factors such as AML1.(5,6) Recently, we and others used gene-targeted mice to reveal critical roles for MOZ in hematopoiesis, particularly in the self-renewal of HSC. (7,8) MOZ fusion genes can also transform HSC and myeloid progenitor cells into leukemia cells and confer unto them self-renewal activity. (9,10) Researching the functions of MOZ and MOZ fusion genes in normal and malignant hematopoiesis can aid in understanding the mechanisms of AML development and leukemic cell-renewal activity. Such discoveries may allow the development of improved AML therapies. Involvement of the MOZ gene in chromosomal translocationsChromosomal translocations, which are frequently detected in patients with AML, include t(8;21), inv(16), t(15;17) and t(11; v) (v: variable) result in the gene fusions AML1-ETO, CBFβ-MYH11, PML-RARα and MLL-fusions, respectively. MOZ was first identified as a gene involved in the translocation t(8;16)(p11;p13) resulting in the MOZ-CBP fusion gene. The MOZ-p300, MOZ-TIF2 and MOZ-NcoA3 fusion genes were later identified in AML from t(8;22)(p11;q13), (12,13) inv(8)(p11;q13) (14,15) and t(8; 20)(p11;q13), (16) respectively (Fig. 1). MOZ is also involved in a patient of pediatric therapy-related myelodysplastic syndrome with a novel chromosomal translocation t(2;8)(p23;p11).(17) MOZ-related factor (MORF; Myst4, Querkopf), a HAT that is highly homologous to MOZ, (18,19) also generates fusion genes with CBP and probably also with Gcn5 in various disorders, including AML (20,21) therapy-related myelodysplastic syndrome (22) and uterine leiomyomata.All MOZ fusion partner genes are involved in histone modification and transcriptional regulation. CBP and p300 are major HAT (24) that function as coactivators for various transcription factors. TIF2 (NcoA2/GRIP1) and NcoA3 (TRAM-1/RAC3/ pCIP/AIB-1) are adaptor proteins that combine nuclear receptors with CBP.(25) AML that express MOZ fusion genes are typically monocytic leukemias classified as M4/M5 among FrenchAmerican-British (FAB) subtypes;(18) MOZ-related translocation is found in about 6.5% of such AML subtypes. (16) In all MOZ fusion genes, breakpoints of MOZ are located in or around its acidic domain (Fig. 1). As a result, the N-terminal region of MOZ is retained and the C-terminal region is replaced with the fusion partners, such as CBP or p300. The N-terminal region of MOZ contains a H15 (histone H1/H5) domain related to nuclear localization, (5) a PHD (plant homeobox-like domain) zinc finger involved in binding to methylated histone,...

show abstract

Acute Mixed Lineage Leukemia With an inv(8)(p11q13) Resulting in Fusion of the Genes for MOZ and TIF2

Cited by 35 publications

References 17 publications

Monocytic Leukemia Zinc Finger (MOZ) Interacts with p53 to Induce p21 Expression and Cell-cycle Arrest

Monocytic Leukemia Zinc Finger (MOZ) Interacts with p53 to Induce p21 Expression and Cell-cycle Arrest

Transcriptional and epigenetic networks in haematological malignancy

Roles of the histone acetyltransferase monocytic leukemia zinc finger protein in normal and malignant hematopoiesis

Contact Info

Product

Resources

About